Since its first Food and Drug Administration (FDA) approval in 1998, deep-brain stimulation (DBS) has gained significant popularity in the treatment of a variety of brain-controlled disorders, including movement disorders [1, 2]. The therapy of the DBS has significant applications in the treatment of tremor, rigidity, and drug induced side effects in patients with Parkinson's disease and essential tremor. Generally, such treatment involves placement of a DBS electrode lead through a burr hole drilled in the patient's skull, followed by placement of the electrode lead and then applying appropriate stimulation signals through the electrode lead to the physiological target. The placement portion of the treatment, involving stereotactic neurosurgical methodology, is very critical, and has been the subject of much attention and research. In particular, finding the deep brain target and then permanently placing the electrode lead so that it efficiently stimulates such target is very important.
Finding the optimal physiological target in deep brain stimulation implants for the treatment of movement disorders is a particularly complicated task. This is especially true for the treatment of symptoms that cannot be tested at the operating table during the electrode lead implantation. For instance, it is practically impossible to test walking and postural stability in Parkinson's Disease (PD) patients during the DSB lead implantation. Two other major PD symptoms, Rigidity and Akinesia, are also considered difficult to evaluate quantitatively during DBS lead implantation. On the other hand, the surgical targets of interest involve deep brain nuclei or subregions within the subthalamus or globus pallidus internus. These structures are not visible in any current imaging modalities, such as magnetic resonance imaging (MRI), X-ray computed tomography (CT), or Positron Emission Tomography (PET).
Ideally, the optimal target for the DBS therapy should be located within the stimulation range of 1 or 2 contacts, each contact measuring 1.5 mm separated by either 1.5 mm or 0.5. Effective stimulation results when the contacts surround the optimal target [3, 4]. For example, for placement of a 4-contact electrode lead of a deep brain stimulator 100, which has a tip portion 170, a central body portion 150 and associated contacts 110, 120, 130 and 140 as shown in FIG. 1, (Medtronic #3387 or #3389 quadripolar lead®, Medtronic, Inc., Minneapolis, Minn.), in the proximity of functional areas which one may refer to as targets or targeted regions, a preferable scenario is that two contacts 110 and 120 of the quadripolar lead 100 lie above and the other contacts 130 and 140 lie below a target. For this example of the lead, each contact 110 (120, 130, 140) has a length, d1, which is substantially around 1.5 mm for a Medtronic #3387 or #3389 quadripolar lead, and the distance between two neighboring contacts, for example, 130 and 140, is d2, where d2=1.5 mm for Medtronic #3387 quadripolar lead, and d2=0.5 mm for Medtronic #3389 quadripolar lead, respectively. If the contacts are located as little as 2 mm away from the desired target, ineffective stimulation results due to several reasons: (i) failure to capture control of the group of neurons, (ii) stimulation of non-desirable areas resulting in unpleasant stimulation, or (iii) necessity for higher stimulus intensities to produce the desired effect resulting in reduced battery life of the implantation, or an any combination of these or other reasons. At least for these reasons, targeting the specific neurons of interest for this therapy requires millimetric precision and allowance for variability among patients. Therefore, the process of implantation of a DBS electrode lead requires stereotactic neurosurgical methodology, i.e., the use of a common reference coordinate system to target structures within the brain. Typically, the process of implantation of a DBS electrode follows a step-wise progression of (i) initial estimation of target localization based on imaged anatomical landmarks, (ii) intra-operative microanatomical mapping of key features associated with the intended target of interest, (iii) adjustment of the final target of implantation by appropriate shifts in three dimensional space, and (iv) implantation of a quadripolar electrode with contacts located surrounding the final desired target.
Because of the invisibility of deep brain targets of interest in any current imaging modalities, such as MRI, CT, or PET, the location of these targets can only be inferred approximately from the position of adjacent structures that are visible in the images. To augment the information that these images provide, printed anatomic atlases or electronic versions of these have been used. Anatomic atlases, such as the Schaltenbrand-Wahren atlas [14], involve a series of unevenly spaced brain sections that have been histologically stained to reveal the structures and substructures of interest. When digitized, these atlases can be superimposed on the pre-operative images using landmarks visible both in the atlas and in the image volumes. Although it represents a partial solution to the target identification problem, this approach suffers from a number of shortcomings [15]. First, available anatomic atlases have been created from one single brain [16] or from several hemispheres pertaining to different individuals [14]. When a single brain is used, information is limited to one sectioning plane per hemisphere. When several brains are used, these atlases show non-contiguous anatomy in intersecting orthogonal slices. Registration (i.e. spatial alignment) of these atlases to the image volumes also raises a number of issues. The standard procedure is to register atlas and image volumes using the inter commisural anterior commissure (AC)-posterior commissure (PC) reference system. This method is one in which the anterior commissure (AC) and posterior commissure (PC) points are manually selected in the images. The volumes are first translated to align the AC points. They are then rotated to align the AC-PC line and the midsagittal planes. Unfortunately, this technique results in substantial misregistration errors. A better approach proposed by St-Jean et al. [17] involves digitizing the Schaltenbrand-Wahren atlas, stacking individual slices, and creating 3D structures from these slices through interpolation. These 3D structures are then registered to one MR image volume by identifying homologous landmarks, thus creating an MR volume on which labels from the atlas can be projected. But, this procedure only guarantees that the landmarks are registered to each other. In a later publication [15], the authors acknowledge that this limitation plus the fact that the creation of the 3D structures involves interpolating 2D atlas slices that can be between 0.5 and 3 mm apart limit the accuracy and therefore the clinical usefulness of this approach.
In current clinical practice, the initial target localization is manually selected on magnetic resonance (MR) images based on anterior commissural (AC)-posterior commissural (PC) coordinates. It can be a lengthy process (sometimes extending for hours in an awake patient) and it requires expertise in neurosurgery, neurophysiology, and clinical neurology [18, 19]. This combined expertise is available only at a limited number of sites, which limits access to the procedure to about 3000 patients per year despite the estimated 180,000 patients per year who would benefit from it in the United States alone.
Therefore, a heretofore unaddressed need exists in the art to address the aforementioned deficiencies and inadequacies.